Efficacy and safety of recombinant human epidermal growth factor for diabetic foot ulcers: A systematic review and meta-analysis of randomised controlled trials.

To evaluate the efficacy and safety of recombinant human epidermal growth factor (rhEGF) in treating diabetic foot ulcers (DFUs), we conducted both database searches (PubMed, MEDLINE, EMBASE, CENTRAL, and Web of Science) and reference searches for randomised controlled trials from the inception of databases to 30 January 2020. Two reviewers independently scrutinised the trials, extracted data, and assessed the quality of trials. The primary outcome was the proportion of complete healing. The secondary outcomes were mean time to complete healing and adverse events. A subgroup analysis was performed by different administration routes. Statistical analyses were performed in RevMan 5.3. The time to complete healing Kaplan-Meier curves was pooled in the R software. Of the 156 citations, 9 trials (720 participants) met eligibility criteria and were included. The rhEGF achieved a higher complete healing rate than placebo (OR: 2.79, [95% CI: 1.99, 3.99]). The rhEGF also significantly shorten complete healing time (MD: -14.10 days, [95% CI: -18.03, -10.16]). Subgroup analysis showed that topical application was superior to intralesional injection, but that may be because of different ulcer severity they included. No significant difference was shown in adverse events. Results were coherent with sensitivity analyses. Therefore, rhEGF is an effective and safe treatment for DFUs.

Human amniotic membrane allograft, a novel treatment for chronic diabetic foot ulcers: A systematic review and meta-analysis of randomised controlled trials.

To evaluate the efficacy and safety of human amniotic membrane (HAM) allograft in treating chronic diabetic foot ulcers (DFUs), a comprehensive search of randomised controlled trials in MEDLINE, EMBASE, PubMed, CENTRAL and Web of Science was conducted to December 7, 2019. Two reviewers independently screened the studies, extracted data, and evaluated the quality of studies. The primary outcome was the proportion of complete healing. The secondary outcomes were mean time to complete healing and adverse events. Statistical analyses were performed using RevMan 5.3. We identified 257 articles, of which 7 articles (465 participants) were included in the meta-analysis. The proportion of complete wound healing in HAM plus standard of care (SOC) group was 3.88 times as high as that in SOC alone (RR: 3.88 [95% CI: 2.34, 6.44]) at 6 weeks, and 2.01 times at 12 weeks (RR: 2.01 [95%CI: 1.45, 2.77]). The intervention group had a significantly shorter time to complete healing (MD: -30.33 days, [95% CI: -37.95, -22.72]). The number needed to treat within 6 weeks was 2.3 ([95% CI: 1.8, 3.1]). No significant difference was shown in adverse events. Results were consistent in a sensitivity analysis. Hence, HAM plus SOC is effective and safe in treating chronic DFUs.

[Atractylenolide I Can Induce Apoptosis of U266 Cells and Enhance Bortezomib Effect].

OBJECTIVE: To investigate the effect of atractylenolide I on proliferation and apoptosis of U266 cells, and anti-multiple myeloma effect of bortezomib. METHODS: Bortezomib, bortezomib combined atractylenolide I and atractylenolide I at different concentrations were added into U266 cells respectively, cellular proliferation toxicity was evaluated by CCK-8 assay, apoptosis and cell cycle were detected by using flow cytometry with Annexin V-FITC/PI staining. RT-PCR and Western blot analysis were used to detect the mRNA and protein levels of targeting gene Caspase-3,Caspase-9,BCL-2,BAX,JAK2,STAT3 and IL-6, respectively. RESULTS: The proliferation of U266 cells could inhibited by atractylenolide I, and the apoptosis of U266 cells could be promoted by atractylenolide I, also, which showed a dose-dependent manner(P<0.00; r=0.99). Moreover, the atractylenolide I could regulat the mitochondrial pathway(P<0.01). The combination of 2 drugs could strengther the inhibition of U266 cell proliferation significantly, and the expression level of IL-6,JAK2,STAT3 and BCL-2 mRNA and protein could be decreased by single drug and 2 drugs both(P<0.01). CONCLUSION: Atractylenolide I significantly inhibits the proliferation of U266 cells and promotes their apoptosis. At the same time, it acts synergistically with bortezomib, which may be related to mitochondrial pathway, and probably related to the regulating of IL-6, JAK2 and STAT3 gene expression in signal pathway of JAK2/STAT3.

MiRNA-140 is a negative feedback regulator of MMP-13 in IL-1ß-stimulated human articular chondrocyte C28/I2 cells.

OBJECTIVE: Osteoarthritis is a degenerative joint disease, in which matrix metalloproteinase (MMP)-13 plays an important role. This study aimed to investigate miRNA-140-mediated negative regulation of MMP-13 expression in interleukin-1ß (IL-1ß)-stimulated human cartilage cells. METHODS: The human cartilage cell line C28/I2 was cultured in the presence of IL-1ß to mimic an osteoarthritic environment. Expression of miRNA-140 and MMP-13 was analyzed after 48 h by real-time RT-PCR and western blot analyses. MiRNA-140 mediated regulation of MMP-13 expression was analyzed by luciferase reporter assays and anti-miRNA-140 oligonucleotide transfection. Furthermore, miRNA-140 and MMP-13 expression was analyzed following DHMEQ treatment. RESULTS: Expression of miRNA-140 and MMP-13 was elevated in IL-1ß-stimulated C28/I2 cells. Bioinformatic prediction showed that the 3'-UTR of MMP-13 mRNA contained a potential binding miRNA-140 site and luciferase mRNA fused with 3'-UTR of MMP-13 mRNA was shown to be repressed by miRNA-140 in reporter assays. Expression of MMP-13 was elevated in IL-1ß-stimulated C28/I2 cells following anti-miRNA-140 oligonucleotide transfection. NF-κB activity was inhibited in DHMEQ treated IL-1ß-stimulated C28/I2 cells and was associated with decreased miRNA-140 and MMP-13 expression. CONCLUSION: Expression of miRNA-140 and MMP-13 was induced by IL-1ß. Expression of miRNA-140 inhibited MMP-13 in C28/I2 cells. Expression of miRNA-140 and MMP-13 was shown to be NF-κB-dependent.